We have developed an electron microscope assay which allows us to measure the association of microtubules with virus particles in vitro. Our results to date indicate that adenovirus interacts with microtubules in a highly specific way, which is easily differentiable from the interactions of control particles. Our experiments also indicate that the hexon capsomer of the virus and the MAPs (Microtubule Associated Proteins) of the microtubules are the interacting species. In support of these points we have observed: (1) in negatively stained preparations, viral hexon capsomers (edges) but not pentons (vertices) are most closely associated with the edge (plus or minus 40A) of the microtubule; (2) pentonless particles bind as avidly to the edge of the microtubule as do viruses; (3) non-infectious virus isolated from a ts mutant (ts 1) which affects the cleavage of virus structural proteins, does not associate in situ with microtubules of infected cells. Current studies are aimed at determining the specific region of interaction between hexons and MAP's.